T ranscriptional regulation of neuron-specific genes by neural restrictive silencer

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We explored potential roles of the neural restrictive silencing factor NRSF/REST in the following four aspects.1.Mechanisms of transcriptional repression by NRSF via direct interaction with general transcriptional core factors : We found that NRSF binds directly to TBP, so that NRSF would be recruited to the core promoter region to repress transcription of its target genes at the promoter site (Murai et al.,2004).2.Structural analysis of the repression domains of NRSF : In collaboration with Prof.Nishimura's group at Yokohama City University, we are in the process of determining the tertiary structure of the two repression domains of NRSF.3.Determination of the target genes of NRSF : In the promoter region of SCLIP gene, we found a silencer-like element that may contribute to the neuron-specific control of SCLIP. We identified that the N-terminal portion of RB3 contributes to the regulation of microtubule dynamics (Nakao et al.,2004). In collaboration with Prof.Miyata's group at Kagoshima, we identified that the neuronal expression of PACAP gene is under the control of NRSF (Sugawara et al.,2004).4.Potential roles of NRSF in non-neural tissues : In a subset of non-small cell lung cancer, NRSF was found to be deregulated by loosing the interaction with BRM or BRG1 subunit of the SWI/SNF complex for chromatin remodeling. This work is a part of collaboration with Prof.Iba's group at Tokyo Iniversity (Watanabe et al.,submitted).